Ralf Schwarzwald

Lateralization of hippocampal activation differs between left and right temporal lobe epilepsy patients and correlates with postsurgical verbal learning decrement

We addressed the question whether lateralization of memory-related medial temporal lobe (MTL) activity in medial temporal lobe epilepsy (MTLE) patients is determined by pathology or sex, differentiating between two MTL subregions implicated in visuospatial memory as regions-of-interest (ROI) - the hippocampus (Hc) and the parahippocampal place area (PPA). We further assessed the relation between lateralization of hippocampal activation and postsurgical memory decline regarding performance in standardized neuropsychological tests of verbal and visuospatial learning. Functional magnetic resonance imaging (fMRI) data were acquired from unilateral MTLE patients performing an object location memory task in a virtual environment. Individual lateralization indices (LI) based on memory-related brain activation patterns were calculated for each subject and ROI. Correlational analyses were computed between pre- to postsurgical changes in learning and asymmetry in hippocampal activation. Results revealed that lateralization of hippocampal, memory-related activity in patients with MTLE was determined by the side of seizure focus, not sex. Laterality of activation in the PPA was neither influenced by side of pathology nor sex. Lateralization of hippocampal activation was significantly correlated with decline in verbal learning after surgery. We were able to demonstrate that asymmetry of hippocampal fMRI-activation in unilateral MTLE patients is determined by the side of seizure focus, thus indicating the relative functional integrity of the hippocampi. This is corroborated by the finding that greater activation of the to-be-resected hippocampus leads to stronger verbal memory decline after surgery.

The reliability of fMRI activations in the medial temporal lobes in a verbal episodic memory task.

The test-retest reliability of activation patterns elicited by encoding and recognition of word-pair associates within the whole brain and a predefined medial temporal region of interest (ROI) was investigated. Twenty healthy right-handed subjects were studied within two sessions, either on the same day or 210-308 days later. Three quantitative measures of reliability were calculated for the contrasts encoding and recognition versus a control condition within the ROI and also for the whole brain: A group correlational analysis between the lateralization indices of the first and second session, correlations of the individual SPM(t) maps of the first and the second run, and overlap ratios between both sessions. For the ROI, correlational analysis of lateralization indices during both encoding trials was significant. Eighty percent of the individual positive correlation coefficients of SPM(t) maps during encoding, and 75% during recognition reached significance. The mean percentage of overlapping voxels was 18% during encoding and 19% during recognition. The reproducibility measures evaluated for the whole brain demonstrated significantly higher values compared to the ROI. For the group that stayed inside the scanner, better whole brain test-retest reliability was observed, and no influence of the memory process (encoding or recognition) on reproducibility was found.

Precuneus is involved in allocentric spatial location encoding and recognition

Using a declarative memory paradigm, the anatomical correlates of spatial location encoding and retrieval in the healthy human brain as reflected by BOLD fMRI were investigated. During encoding, subjects were instructed to view and keep in mind different locations of an object on a platform seen from different viewpoints in virtual 3D. In retrieval trials, subjects had to recognize previously learned object locations. Comparing activation patterns associated with encoding and recognition on a voxel-by-voxel basis, we found regions in the precuneus bilaterally activated by both processes. To our knowledge, this is the first study that directly compared human brain activation patterns associated with allocentric encoding and retrieval of spatial locations in virtual 3D. Our results provide further information concerning the role of the precuneus in declarative memory processes, pointing to precuneus involvement in encoding and retrieval of spatial locations.

The influence of sex differences and individual task performance on brain activation during planning.

Several studies have attempted to identify the neuronal basis of sex differences in cognition. However, group differences in cognitive ability rather than genuine neurocognitive differences between the sexes may account for their results. Here, we compare with functional magnetic resonance imaging the relation between gender, individual task performance, and planning-related brain activation. Men and women preselected to display identical performance scores showed a strong relation between individual task performance and activation of the right dorsolateral prefrontal and right inferior parietal cortex activation during a visuospatial planning task. No gender-specific activations were found. However, a different pattern emerged when subjects had to execute the motor responses to the problems. Better performance was associated with right dorsolateral prefrontal and right parahippocampal activations, and females exhibited a stronger right hippocampal activation than males. These findings underline that an individuals performance level rather than his or her sex largely determines the neuronal activation patterns during higher-level cognition.

Who needs a Wada test? Present clinical indications for amobarbital procedures

Introduction The Wada test has been the gold standard for testing cerebral language localisation during presurgical investigation in the past decades. However, during the last few years a shift has occurred in epilepsy surgery programmes towards the use of non-invasive methods, predominantly functional MRI (fMRI). However, Wada tests are still performed, albeit in a considerably smaller number of patients at many epilepsy centres. Methods A retrospective monocentric analysis of remaining clinical indications for performing a Wada procedure was undertaken. The clinical data of patients who participated in Wada tests (42 hemispheric and 8 superselective procedures) during recent years were retrospectively evaluated. Results Reasons for conducting a Wada test were (1) a patients inability to perform the fMRI task due to agitation, mental disablement, or perceptual impairment, (2) validation of atypical, inconclusive or not clearly lateralised language activation shown with fMRI, (3) evaluation of propagation of ongoing interictal bilateral epileptiform EEG activity, (4) region selective testing of language and other cognitive functions, or (5) assessment of motor localisation. Patients who were not able to perform the fMRI task or in whom fMRI did not provide interpretable results were significantly younger (p<0.05). Conclusion It is argued that fMRI is eligible to replace Wada tests in the majority of patients who are compliant with clearly lateralised language localisation, but in patients who are agitated or mentally impaired as well as in the case of the above-mentioned specific clinical indications and bilateral fMRI activations, Wada tests still provide additional information. Additionally, non-invasive methods less sensitive to movement artefacts are discussed as possible alternatives for these patients.

Tracking the subprocesses of decision-based action in the human frontal lobes

Situationally adaptive behavior relies on the identification of relevant target stimuli, the evaluation of these with respect to the current context and the selection of an appropriate action. We used functional magnetic resonance imaging (fMRI) to disentangle the neural networks underlying these processes within a single task. Our results show that activation of mid-ventrolateral prefrontal cortex (PFC) reflects the perceived presence of a target stimulus regardless of context, whereas context-appropriate evaluation is subserved by mid-dorsolateral PFC. Enhancing demands on response selection by means of response conflict activated a network of regions, all of which are directly connected to motor areas. On the midline, rostral anterior paracingulate cortex was found to link target detection and response selection by monitoring for the presence of behaviorally significant conditions. In summary, we provide new evidence for process-specific functional dissociations in the frontal lobes. In target-centered processing, target detection in the VLPFC is separable from contextual evaluation in the DLPFC. Response-centered processing in motor-associated regions occurs partly in parallel to these processes, which may enhance behavioral efficiency, but it may also lead to reaction time increases when an irrelevant response tendency is elicited.

Late-onset autosomal dominant limb girdle muscular dystrophy and Paget's disease of bone unlinked to the VCP gene locus.

The broadwide spectrum of differential diagnoses of autosomal dominant muscular dystrophies in adults can be specified by additional features. The combination of late-onset muscular dystrophy, rimmed vacuoles and inclusion bodies in the muscle biopsy, and Pagets disease of bone suggests a mutation in the Valosin-containing protein gene (VCP, p97 or CDC48) even without dementia. We report on a German family with late-onset autosomal dominant muscular dystrophy starting in the pelvic girdle about age 40years, a subsequent rapidly-progressing course, high alkaline phosphatase and Pagets disease of bone. Clinical examination revealed no cognitive impairment. Histology showed myopathic changes with rimmed vacuoles and inclusion bodies on muscle biopsy. Mutations in VCP, filamin C, desmin, alphaB-crystallin, ZASP and myosin heavy chains 2 and 7 as well as the genes for facioscapulohumeral muscular dystrophy, Myotonic Dystrophy I and II, and LGMD1A-G were excluded by a combination of linkage analysis and direct sequencing. The family presented here suggests that a yet-unknown genetic defect can give rise to an autosomal dominant myopathy with Pagets disease but without dementia.

Stellenwert der fMRT zur Bestimmung der zerebralen Sprachdominanz

ZusammenfassungDie Bestimmung der zerebralen Sprachrepräsentation ist wesentlicher Bestandteil der prächirurgischen Diagnostik vor Operationen in potentiell sprachrelevanten Regionen, insbesondere vor elektiven epilepsiechirurgischen Eingriffen. Die etablierten Verfahren Wada-Test und kortikale Stimulation sind invasiv und belastend. Seit ca. 10 Jahren steht die funktionelle Magnetresonanztomographie (fMRT) als nichtinvasive Alternative zur Verfügung. Obwohl in zahlreichen Untersuchungen eine gute Übereinstimmung der Ergebnisse von fMRT und Wada-Test gezeigt werden konnte, gibt es keine allgemein akzeptierten Empfehlungen, in welchen Fällen auf einen Wada-Test verzichtet werden kann. In der vorliegenden Zusammenstellung untersuchten die Autoren, wie sich das diagnostische Procedere seit der klinischen Einführung der Sprach-fMRT an ihrer Institution verändert hat. Seit 1999 wurden in Freiburg 208 Sprach-fMRTs bei 198 Patienten durchgeführt. Im gleichen Zeitraum reduzierte sich der relative Anteil der Patienten der Sektion Prächirurgische Epilepsiediagnostik, bei denen ein Wada-Test durchgeführt wurde, um ca. 50%. Der Anteil der Sprach-fMRTs, der vorwiegend aufgrund mangelhafter Kooperationsfähigkeit der Patienten nicht verwertbar war, lag in den vergangenen 2 Jahren < 10%. Nach Ansicht der Autoren besteht lediglich noch in den Fällen eine zwingende Indikation für einen Wada-Test, in denen keine Sprach-fMRT durchführbar ist oder die fMRT therapeutisch entscheidende Fragen nicht beantworten kann.AbstractDetermination of hemispheric language dominance is an essential step in the diagnostic workup prior to surgery in brain regions potentially involved in language. The established methods Wada test and cortical stimulation are invasive and cumbersome. For a decade, functional magnetic resonance imaging (fMRI) has allowed for the noninvasive determination of cerebral language representation. Numerous studies have shown good correlation between the results of language fMRI and invasive procedures. However, there are no generally accepted proposals in which cases invasive diagnostic procedures might be dispensable. The authors studied how the diagnostic regimen has changed in their institution since the clinical implementation of language fMRI. Since 1999, 208 language fMRIs have been performed in 198 patients in Freiburg. During this period the percentage of patients at the Department of Presurgical Epilepsy Diagnosis receiving a Wada test decreased by 50%. In the last 2 years < 10% of the fMRIs were not utilizable, most often due to motion artifacts. In the authors’ opinion fMRI should be the diagnostic method of first choice in all patients in whom surgery is planned in brain regions potentially involved in language. Only if further questions of therapeutic relevance are present, additional invasive procedures are mandatory.